Raloxifene decreases cell viability and migratory potential in prostate cancer cells (LNCaP) with GPR30/GPER1 involvement

Abstract

Objectives This study evaluated raloxifene (ral) effects on LNCaP prostate tumour cells modulating the activity of GPER1/GPR30 receptors. Methods LNCaP cells were submitted for 40/120 min and 12 h to the following treatments: C: RPMI + DMSO; R: RPMI + Ral; G: RPMI + Ral + G15 (GPER1 antagonist). Trypan blue staining measured cell viability. Migratory potential (12 h) was measured by transwell migration test in translucent inserts, which were then stained with DAPI and analysed under a fluorescence microscope for quantification. Cells from 40-and 120-min treatments were subjected to protein extraction to the study of AKT, pAKT, ERK, pERK, ERb and SIRT1. Key findings There is a reduction in cellular viability in R compared to C at all evaluated times, and an increased cell viability in G when compared to R; cell viability was similar in C and G in all times studied. The migration assay demonstrated a significant decrease in migration potential of tumour cells in R compared to C and G. Ral treatment reduced pERK expression and increased pAKT in the treated groups after 40 min, pointing out to an antiproliferative and apoptotic effect in the GPER1-controlled rapid-effect pathways. Conclusions Raloxifene was able to modulate GPER1 in LNCaP prostate tumour cells, decreasing cell viability and their migratory potential.

GPER1 Silencing Suppresses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Inhibiting PI3K/AKT–Mediated EMT

“…However, GPER1 has contradictory roles as either a tumor-suppressor or a tumor-promoter in, depending on the specific cancer context. GPER1 acts as a tumor promoter in thyroid cancer (Manfroi et al, 2020), hepatocellular carcinoma (Chaturantabut et al, 2019), and renal cell adenocarcinoma (Feldman et al, 2016), whereas GPER1 can inhibit the proliferation of lung cancer (Narayanankutty, 2019), prostate cancer (Salata et al, 2019), and estrogen receptor-negative breast cancer cells (Wei et al, 2014). The roles of GPER1 in gastric cancer (GC) have not been fully clarified.…”

Effects of a phthalate metabolite mixture on both normal and tumoral human prostate cells

“…Cells crossing the membrane were fixed with methanol and stained with 0.1% hematoxylin for visualization. Cells were counted in four fields at 400× amplification using an inverted light microscope (Zeiss Axiovert®, Germany) 15 …”

“…Limitations in diagnostic methods to detection and staging of prostate result in low detections at early stages, and thus, many men with undiagnosed cancer are exposed to environmental factors that can accelerate the growth and malignancy of tumors 14 . Thus, this study was designed to clarify the behavior of LNCaP cells, representing late pathologies, and PNT‐2 cells, representing a normal group, in response to exposure to specific doses of a mixture of phthalate metabolites and to elucidate phthalate‐induced changes in gene modulation pathways related to cell survival, stress, and modulation of epigenetic mechanisms 15 . We proposed that an environmentally relevant phthalate metabolite mixture alters molecular parameters in both normal and cancer cells and establishes an environment favorable to the growth and aggressiveness of tumor cells.…”

Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development

“…The formulation effects on cell migration were investigated using T-47D cells placed in migration inserts (a density of 1 × 10 4 cells, Nunc, Thermo Fischer Scientific, Waltham, MA, USA) containing 300 μL of FBS-free DMEM GlutaMAX. In each well of the 24-well culture plates, 600 μL of the medium with 10% FBS was added for the chemoattractive role …”

“…On the day of the experiment, each insert was either untreated (maintained with the FBS-free medium) or treated (as described above) for 24 h with the unloaded ME or ME containing fenretinide (1%, ME-F) at the concentration equivalent to IC 15 for 24 h. After treatment, the migration inserts were collected, and cells that were unable to migrate through pores and remained in the upper part of the membrane were gently removed with cotton swab . Cells that migrated through the pores were fixed for 10 min in cold methanol 100% and stained in a dark environment with Fluoroshield solution with DAPI.…”